Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma

Rezaul Karim, Ekaterina S. Jordanova, Sytse J. Piersma, Gemma G. Kenter, Lieping Chen, Judith M. Boer, Cornelis J M Melief, Sjoerd H. Van Der Burg

Research output: Contribution to journalArticle

Abstract

Purpose: The interaction between programmed cell death 1 (PD-1), expressed by activated effector or regulatory T cells, and B7-H1 (PD-L1) and B7-DC (PD-L2) results in the inhibition of T-cell function. The aim of this study was to determine B7-H1, B7-DC, and PD-1 expression in cervical carcinoma. Experimental Design: A tissue microarray of a well-defined groupof 115 patients was stained with antibodies against B7-H1 and B7-DC. Three-color fluorescent immunohistochemistry was used to study the number and phenotype of tumor-infiltrating T cells expressing PD-1. Additional analyses consisted of in vitro T-cell suppression assays. Results: B7-H1 was expressed in 19%, and B7-DC was expressed by 29% of the 115 tumors. PD-1 was expressed by more than half of both the infiltrating CD8+ T cells and CD4+Foxp3+ T cells, irrespective of B7-H1 or B7-DC expression by tumors. The expression of B7-H1 did not show a direct impact on patient survival. However, subgroup analysis revealed that patients with a relative excess of infiltrating regulatory T cells displayed a better survival when the tumor was B7-H1 positive (P = 0.033). Additional studies showed that the presence of B7-H1 during the activation of CD4+Foxp3+ regulatory T cells impaired their suppressive function in a functional in vitro assay. Conclusions: B7-H1 is expressed on only a minority of cervical cancers and does not influence the survival of patients with cervical cancer. PD-1 is expressed by a vast number of infiltrating CD8 T cells, suggesting that blocking of PD-1 could have therapeutic potential in cervical cancer patients.

Original languageEnglish (US)
Pages (from-to)6341-6347
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number20
DOIs
StatePublished - Oct 15 2009

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Cell Survival
Cell Death
Carcinoma
T-Lymphocytes
Regulatory T-Lymphocytes
Uterine Cervical Neoplasms
Neoplasms
Survival
Research Design
Color
Immunohistochemistry
Phenotype
Antibodies
In Vitro Techniques
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Karim, R., Jordanova, E. S., Piersma, S. J., Kenter, G. G., Chen, L., Boer, J. M., ... Van Der Burg, S. H. (2009). Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma. Clinical Cancer Research, 15(20), 6341-6347. https://doi.org/10.1158/1078-0432.CCR-09-1652

Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma. / Karim, Rezaul; Jordanova, Ekaterina S.; Piersma, Sytse J.; Kenter, Gemma G.; Chen, Lieping; Boer, Judith M.; Melief, Cornelis J M; Van Der Burg, Sjoerd H.

In: Clinical Cancer Research, Vol. 15, No. 20, 15.10.2009, p. 6341-6347.

Research output: Contribution to journalArticle

Karim, R, Jordanova, ES, Piersma, SJ, Kenter, GG, Chen, L, Boer, JM, Melief, CJM & Van Der Burg, SH 2009, 'Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma', Clinical Cancer Research, vol. 15, no. 20, pp. 6341-6347. https://doi.org/10.1158/1078-0432.CCR-09-1652
Karim, Rezaul ; Jordanova, Ekaterina S. ; Piersma, Sytse J. ; Kenter, Gemma G. ; Chen, Lieping ; Boer, Judith M. ; Melief, Cornelis J M ; Van Der Burg, Sjoerd H. / Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 20. pp. 6341-6347.
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abstract = "Purpose: The interaction between programmed cell death 1 (PD-1), expressed by activated effector or regulatory T cells, and B7-H1 (PD-L1) and B7-DC (PD-L2) results in the inhibition of T-cell function. The aim of this study was to determine B7-H1, B7-DC, and PD-1 expression in cervical carcinoma. Experimental Design: A tissue microarray of a well-defined groupof 115 patients was stained with antibodies against B7-H1 and B7-DC. Three-color fluorescent immunohistochemistry was used to study the number and phenotype of tumor-infiltrating T cells expressing PD-1. Additional analyses consisted of in vitro T-cell suppression assays. Results: B7-H1 was expressed in 19{\%}, and B7-DC was expressed by 29{\%} of the 115 tumors. PD-1 was expressed by more than half of both the infiltrating CD8+ T cells and CD4+Foxp3+ T cells, irrespective of B7-H1 or B7-DC expression by tumors. The expression of B7-H1 did not show a direct impact on patient survival. However, subgroup analysis revealed that patients with a relative excess of infiltrating regulatory T cells displayed a better survival when the tumor was B7-H1 positive (P = 0.033). Additional studies showed that the presence of B7-H1 during the activation of CD4+Foxp3+ regulatory T cells impaired their suppressive function in a functional in vitro assay. Conclusions: B7-H1 is expressed on only a minority of cervical cancers and does not influence the survival of patients with cervical cancer. PD-1 is expressed by a vast number of infiltrating CD8 T cells, suggesting that blocking of PD-1 could have therapeutic potential in cervical cancer patients.",
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AU - Karim, Rezaul

AU - Jordanova, Ekaterina S.

AU - Piersma, Sytse J.

AU - Kenter, Gemma G.

AU - Chen, Lieping

AU - Boer, Judith M.

AU - Melief, Cornelis J M

AU - Van Der Burg, Sjoerd H.

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N2 - Purpose: The interaction between programmed cell death 1 (PD-1), expressed by activated effector or regulatory T cells, and B7-H1 (PD-L1) and B7-DC (PD-L2) results in the inhibition of T-cell function. The aim of this study was to determine B7-H1, B7-DC, and PD-1 expression in cervical carcinoma. Experimental Design: A tissue microarray of a well-defined groupof 115 patients was stained with antibodies against B7-H1 and B7-DC. Three-color fluorescent immunohistochemistry was used to study the number and phenotype of tumor-infiltrating T cells expressing PD-1. Additional analyses consisted of in vitro T-cell suppression assays. Results: B7-H1 was expressed in 19%, and B7-DC was expressed by 29% of the 115 tumors. PD-1 was expressed by more than half of both the infiltrating CD8+ T cells and CD4+Foxp3+ T cells, irrespective of B7-H1 or B7-DC expression by tumors. The expression of B7-H1 did not show a direct impact on patient survival. However, subgroup analysis revealed that patients with a relative excess of infiltrating regulatory T cells displayed a better survival when the tumor was B7-H1 positive (P = 0.033). Additional studies showed that the presence of B7-H1 during the activation of CD4+Foxp3+ regulatory T cells impaired their suppressive function in a functional in vitro assay. Conclusions: B7-H1 is expressed on only a minority of cervical cancers and does not influence the survival of patients with cervical cancer. PD-1 is expressed by a vast number of infiltrating CD8 T cells, suggesting that blocking of PD-1 could have therapeutic potential in cervical cancer patients.

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